PGK2
protein-codingphosphoglycerate kinase 2
Gene summary
This gene is intronless, arose via retrotransposition of the phosphoglycerate kinase 1 gene, and is expressed specifically in the testis. Initially assumed to be a pseudogene, the encoded protein is actually a functional phosphoglycerate kinase that catalyzes the reversible conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate, during the Embden-Meyerhof-Parnas pathway of glycolysis, in the later stages of spermatogenesis.[provided by RefSeq, May 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0018393
Submitter: King Faisal Specialist Hospital and Research Center
Alhathal et al., 2020 (PMID: 32719396) reported a missense variant in a large male infertility cohort (n=285 infertile man and case–control fertile man). Gene is scored according to ClinGen classification. Moderate with total score of 8. Single-variant analysis (3 points), experimental evidence: Animal model (4 points) and testicular expression (1 points) (PMID: 19759366).
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PGK2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_138733.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 70 | 70 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 70 | 0 | 0 | 70 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_620061.2 | 1 | MANE Select | |
| Ensembl | ENSP00000305995.3 | 1 | MANE Select | |
| Ensembl | ENSP00000799402.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycolysis / Gluconeogenesis - Homo sapiens (human)
- Cori Cycle
- Pathways in clear cell renal cell carcinoma
- Glycolysis and Gluconeogenesis
- Metabolism of carbohydrates
Biological Process
- gluconeogenesis
- glycolytic process
- phosphorylation
- positive regulation of oxidative phosphorylation
Molecular Function
- phosphoglycerate kinase activity
- ATP binding
- ADP binding
Cellular Component
- nucleus
- cytosol
- sperm fibrous sheath
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000304801
- Coding exons
- 1
- Length
- 1688
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.921 | 257 | 219 | 1.18 | 0.0000111 | 2747 |
| Missense (PolyPhen) | 79 | 76.778 | 1.0289 | 971 | ||
| Synonymous | -1.68 | 101 | 81.7 | 1.24 | 0.00000449 | 850 |
| Loss of Function | 0.242 | 8 | 8.77 | 0.912 | 5.50e-7 | 126 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Essential for sperm motility and male fertility (PubMed:26677959). Not required for the completion of spermatogenesis (By similarity). {ECO:0000250|UniProtKB:P09041, ECO:0000269|PubMed:26677959}.;
Recessive Scores
- pRec
- 0.503
Intolerance Scores
- LoFtool
- 0.165
- RVIS EVS
- 0.42
- RVIS percentile EVS
- 77.06
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.966
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |